Purification processes such as distillation, chromatography, and liquid-liquid extraction are widely employed in the purification of chemical compounds. Distillation involves heating the components in a mixture, which may cause chemical degradation of the compound of interest. Chromatographic techniques are generally batch-type processes that are difficult to scale-up. Liquid--liquid extraction generally relies on selective transfer of solute between two immiscible solutions to accomplish purification of the transferring component. In most cases, immiscible solution pairs used in liquid-liquid extraction include one aqueous and one organic solution.
Traditional liquid-liquid extraction methods and apparatus require a significant density difference between solution pairs to achieve complete separation of the liquids and efficient recovery of transferring component(s). The use of this method of purifying components is complicated by the need to identify immiscible solution pairs between which the desired product component is transferred with a high degree of selectivity, and which can be easily separated once solute transfer is achieved. Selectivity refers to the property whereby the desired component is effectively transferred between immiscible solutions, whereas other components initially present in solution with the transferring component are not transferred.
Aqueous two phase partitioning (ATPP) liquid-liquid extraction systems have shown considerable potential for separation of some classes of compounds. Aqueous two phase partitioning systems are prepared by dissolving soluble polymers, such as polyethylene glycol (PEG) or dextran (DEX) in water. ATPP systems can also be formed by adding a soluble polymer and a soluble, low molecular weight compound (typically an inorganic salt) to water. When these types of chemicals are added to water in certain concentrations and are thoroughly dispersed by mixing or agitation, a turbid emulsion is formed which separates into two distinct liquid phases upon standing. Separation of the emulsion into two phases of differing composition results from incompatibilities between the water-soluble polymers or between a polymer and a salt. The difference in density between the two phases is typically very small. U.S. Pat. No. 4,579,661 discloses purification of a biologically active substance by extraction using at least two aqueous phases, one of which comprises an insoluble particle having affinity for the biologically active substance. U.S. Pat. No. 5,093,254 discloses an aqueous two-phase protein partitioning system that uses a ligand-polymer complex to enhance transfer of the biological material of interest to the phase comprising the complex. The two patent methods are examples of aqueous two phase partitioning systems of solutions of near equal density. Recently, ATPP systems have been applied for the recovery of 99m Technetium (.sup.99m Tc). Other potential applications of ATPP systems include, but are not limited to, environmental restoration and waste management activities.
Despite the promise that ATPP systems hold for the purification of chemicals, application of such systems has been limited due to processing difficulties. Typically, density differences between solutions in ATPP systems are small, because the solutions consist primarily of water. Efficient transfer and recovery of components in liquid--liquid extraction processes requires the intimate mixing of the liquid phases to promote transfer of the component of interest, followed by complete separation of the mixture into its component liquid phases. Conventional extraction apparatus require relatively large volumes of working solutions, and are slow to reach mass transfer equilibrium. In addition, these apparatus generally rely on gravity settling for separation of the ATPP system dispersion.
Because solutions in ATPP systems have nearly equal densities, phase separations by gravity are slow and inefficient. Failure to obtain complete phase separation after transfer results in carryover of impurities into the product phase and retention of the component of interest in the waste phase. To overcome the phase separation problem, current ATPP applications employ separate equipment pieces for mixing and separation of the solution pairs. In one conventional process embodiment, the phases are mixed in one vessel to achieve transfer of the component of interest, and are then transferred by pumping to an apparatus that separates the dispersion by the application of centrifugal force. One or more holding vessels may be located between the mixing and separating apparatus to accommodate fluctuations in process parameters. Use of multiple steps and equipment pieces increases the overall cost of the purification operation, and increases the risk of introducing contaminants into the product stream.
Advanced centrifugal contactors have been disclosed that offer the advantages of increased recovery of desired material, high throughput, high mass transfer efficiency, rapid attainment of steady state, and a modular design that facilitates maintenance (U.S. Pat. Nos. 4,925,441 and 5,024,647). However, these contactors have been used exclusively for applications that employ extractions between organic and aqueous phases with large differences in phase density.
What is needed in the art is a means of improving the separation attainable between solutions of near equal density.